The disclosure relates in general to the field of microfluidic probe devices, and in particular, to a microfluidic probe head and a method of fabrication thereof.
Microfluidics generally refers to microfabricated devices, which are used for pumping, sampling, mixing, analyzing and dosing liquids. Prominent features thereof originate from the peculiar behavior that liquids exhibit at the micrometer length scale. Flow of liquids in microfluidics is typically laminar. Volumes well below one nanoliter can be reached by fabricating structures with lateral dimensions in the micrometer range. Reactions that are limited at large scales (by diffusion of reactants) can be accelerated. Finally, parallel streams of liquids can possibly be accurately and reproducibility controlled, allowing for chemical reactions and gradients to be made at liquid/liquid and liquid/solid interfaces. Microfluidics are accordingly used for various applications in life sciences.
Most microfluidic devices have user chip interfaces and closed flow paths. Closed flow paths facilitate the integration of functional elements (e.g., heaters, mixers, pumps, UV detector, valves, etc.) into one device while minimizing problems related to leaks and evaporation. However, processing or patterning surfaces with such microfluidics is hard to achieve.
Inkjets were designed which can for instance deliver ink in a non-contact mode but not in the presence of an immersion liquid. Other techniques can further pattern surfaces at even higher resolution but are limited in their ability to operate in a liquid environment. Liquid environments minimize drying artifacts, denaturation of biomolecules, and enable working with living microorganisms.
For patterning surfaces and analyzing samples on a surface in the presence of a liquid environment, several strategies were developed to overcome limitations of closed microfluidics. Some strategies rely on confining liquids near a surface or, still, delivering a precise amount of biomolecules in a well defined region of a liquid. Scanning nanopipettes and hollow Atomic Force Microscopy (AFM) probes were also developed for patterning biomolecules on surfaces with micrometer accuracy.
As an other example, a non-contact microfluidic probe technology (or “MFP”) was developed (see, e.g., US 2005/0247673), which allows to pattern surfaces by adding or removing biomolecules, create surface density gradients of proteins deposited on surfaces, localize reactions at liquid interphases in proximity to a surface, stain and remove adherent cells on a surface. Other applications have been tested.
FIGS. 1A-D depict such a MFP head 100 and further illustrate its working principle. The part 105 (FIG. 1D) of the head 100 that confines the liquid is a Si chip that has two apertures 101, 102. It is brought close to a substrate 300 of interest. Horizontal microchannels 115 (FIG. 1C) on the other face of the chip 100 link the apertures with vias 91, 92 formed in a poly(dimethylsiloxane) (PDMS) connection block 90, FIG. 1A. Capillaries 81, 82 inserted in the PDMS provide connection between motorized pumps and apertures 101, 102. Therefore, by controlling the flow rate of a liquid 420 injected through one aperture 101 and by reaspirating it from the other aperture 102 (together with some of the immersion liquid 410), confinement of the injected liquid 420 is achieved, FIG. 1D. Such an MFP head as assembled is schematically depicted in FIG. 1C.
Although this MFP technology is advantageous in many respects and for a range of applications, challenges remain to be solved in terms of fabrication. In particular, assembling the Si head 100 with the PDMS connection block 90 and inserting the glass capillaries 81, 82 is labor intensive. Such operations also have limited yield because the Si chip and PDMS are small and difficult to handle. In addition, stress in the PDMS block 90 during bonding to the Si head and insertion of the capillaries can lead to the detachment of the PDMS. Moreover, micro fabricating small apertures in a thick Si wafer using e.g., deep reactive ion etching (DRIE) or plasma etching, is likely challenging and time consuming, owing to the thickness that the head must have for e.g., mechanical stability. Such limitations may hinder the industrialized deployment of MFP technology.
For the sake of completeness, US 2007/0160502, JP 2005/111567 and U.S. Pat. No. 5,882,465 also deal with processes of fabrication of microfluidic devices or reactors.